Disconnected Out of Passion: Relationship Between Social Alienation and Obsessive Passion.

Violent radicalization continues to be a global problem. One of the main proposals for understanding radicalization and support for political violence is based on social alienation as a trigger. That is, individuals who feel alienated from society try to get out of this situation by using violence, if necessary. However, social alienation alone is not enough to explain radicalization. Therefore, we propose that social alienation interacts with other factors to foster radicalization. Particularly, we propose that obsessive passion, an internal compulsion that leads a person to engage in an activity even when they should not, is one of the interacting factors. Following previous literature, we hypothesized that higher social alienation predicts support for political violence to a greater extent the higher the obsessive passion. To test this hypothesis, we performed two studies in which the cause of passion varied (religion: N = 652 and family: N = 873). Both studies assessed social alienation, harmonious and obsessive passion, and support for political violence. The results showed a significant increase in the effect of social alienation on support for political violence when obsessive passion was higher, even controlling by harmonious passion. These results highlight the importance of considering other variables related to social alienation that could facilitate radicalization processes, particularly maintaining an obsessive passion for a cause when one feels a social disconnection. The theoretical and practical implications of these results are discussed given their contributions to prevention based on work on feelings of social disconnection and harmonization of causes.

Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial.

HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) vaccine immunogen designed to elicit cellular immune responses to HIV targets associated with viral control in humans. The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Secondary objectives included T-cell immunogenicity, the effect on viral rebound and the safety of an antiretroviral treatment interruption (ATI). Adverse events were mostly mild and transient. No related serious adverse events were observed. We show here that HTI vaccines were able to induce strong, polyfunctional and broad CD4 and CD8 T-cell responses. All participants experienced detectable viral rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either >100,000 copies ml-1, >10,000 copies ml-1 for eight consecutive weeks, or after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a prolonged time off ART in vaccinees without beneficial HLA (human leukocyte antigen) class I alleles. Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials.

Use of fourth-generation rapid combined antigen and antibody diagnostic tests for the detection of acute HIV infection in a community centre for men who have sex with men, between 2016 and 2019.

OBJECTIVE: To assess the use of fourth-generation rapid diagnostic tests in identifying acute infection of Human Immunodeficiency Virus (HIV). METHODS: BCN Checkpoint promotes sexual health among men who have sex with men (MSM), with a focus on diagnosing HIV early, initiating combined antiretroviral treatment (cART) promptly, and recommending regular repeat testing for those who have tested negative. This cross-sectional study included all test results obtained at the centre between 25 March 2016 and 24 March 2019. The Alere™ HIV Combo (now rebranded to Determine™ HIV Ultra, from Abbott) was used to detect p24 antigen (p24 Ag) and/or immunoglobulin M (IgM) and G (IgG) antibodies to HIV-1/HIV-2 (HIV Ab). Rapid polymerase chain reaction (PCR) confirmatory testing and Western blot (WB) were performed for clients with a positive rapid test result. Confirmed HIV cases were promptly referred to the HIV unit for care and cART prescription. RESULTS: A total of 12,961 clients attended BCN Checkpoint during the study and 27,298 rapid tests were performed. 450 tests were found to be reactive, of which 430 confirmed as HIV-positive, representing a prevalence of 3.32%. Four confirmed cases (0.93%) were detected as "p24 Ag only", nine (2.09%) as "both p24 and HIV Ab" and 417 (96.98%) as "HIV Ab only". The "p24 Ag only" group had a 1-log higher viral load than the other groups and initiated treatment on the following working day. Overall, there were 20 false-positive results (0.07% and 4.44% of total and reactive tests, respectively), of which 10 positive for "p24 Ag only" and 10 for "HIV Ab only". CONCLUSIONS: Four Acute HIV Infections (AHI), with very high viral loads, have been detected with the "p24 Ag only" while the HIV Ab were still absent. Referral to the HIV unit and initiation of cART on the following working day contributed to improving persons' health and to reduce HIV transmission chain.

Falling HIV incidence in a community clinic cohort of men who have sex with men and transgender women in Barcelona, Spain.

In Barcelona, Spain prior to 2006, HIV testing was mostly limited to formal healthcare facilities with no incidence data reported. A community-based organization (BCN Checkpoint) was established to increase HIV testing in a peer-led community location to generate incidence data in men who have sex with men and transgender women. Three community engagement interventions were conducted between 2009 and 2017 as follows: 2009-2011 (peer-led point-of-care testing for HIV), 2012-2014 (12-monthly HIV testing with an emphasis on testing in partnerships), 2015-2017 (three-monthly HIV testing with rapid referral for antiretroviral initiation). Between 2009 and 2017 a predominantly cisgender male (99.4%) and Spanish national (62.4%) population with mean age of 34.8 years had 49,630 visits. Mean visit number increased from 1.69 in the first to 2.07 in the last three-year period. HIV incidence fell from 4.17 (95% confidence interval [CI]: 3.53-4.93) per 100 person-years in 2009-2011 to 1.57 (95% CI: 1.30-1.89) per 100 person-years in 2015-2017. This represents a 62% reduction (incidence rate ratio: 0.38, 95% CI: 0.29-0.48) between the first and third study period (p < 0.001). These early interventions may have contributed to the reduction seen in HIV incidence in this cohort.

Attachment Styles, Condomless Sex, and Drugs in HIV-Positive Gay and Bisexual Men.

This study evaluated whether attachment styles might be related to condomless sex, use of drugs, and adherence to antiretroviral treatment (ART) in 400 HIV-positive gay and bisexual men (GBM). With the Relationship Questionnaire, 160 men were classified as securely attached and 240 as insecurely attached (88 dismissive, 79 preoccupied, and 73 fearful). Insecurely attached GBM had more condomless sex (p = 0.04), and used more cocaine (p = 0.001), ecstasy (p = 0.03), GHB (p = 0.04), and ketamine (p = 0.04). No differences were observed in adherence to ART. Dismissively attached GBM reported more condomless sex and use of drugs than preoccupied and fearfully attached GBM. The perspective of attachment might enrich the interventions to promote heath care in GBM.

Sexually transmitted infections in young people and factors associated with HIV coinfection: an observational study in a large city.

OBJECTIVES: Young people are a critical target group for sexually transmitted infections (STI) surveillance due to their particular behavioural and social related vulnerability. The aim of this study was to describe the epidemiological characteristics and trends in the incidence of gonorrhoea, syphilis, HIV and venereal lymphogranuloma (LGV) among 15-24-year-olds in Barcelona, and to determine factors associated with HIV coinfection. DESIGN: We performed a population-based incidence study covering the 2007-2015 period. PARTICIPANTS: All new cases of STI-HIV, gonorrhoea, infectious syphilis and LGV-notified to the epidemiological surveillance system in Barcelona between 2007 and 2015. 1218 cases were studied: 84.6% were men, 19.3% were 15-19 years old and 50.6% were born in Spain. Among men, 73.7% were men who have sex with men (MSM); among women, 85.6% were women that have sex with men. PRIMARY AND SECONDARY OUTCOMES: Incidence of HIV, gonorrhoea, infectious syphilis and LGV. HIV coinfection. RESULTS: There was an increase in the incidence of gonorrhoea, from 1.9 cases per 10 000 people in 2007 to 7.6/10 000 in 2015 (p<0.01), in MSM from 27.1 to 228.8/10 000 (p<0.01). The incidence of syphilis increased from 0.4/10 000 in 2007 to 3.1/10 000 in 2015 (significant in men only, p<0.01), in MSM from 18.1 to 116.9/10 000 (p<0.01). The incidence of HIV showed a non-significant increase in men (p=0.27), and that of LGV remained stable (p=0.59). Factors associated with increased risk of HIV coinfection included being MSM (adjusted OR[ORa]=14.14, 95% CI 3.34 to 59.91) and having >10 sexual partners (ORa=4.11, 95% CI 1.53 to 11.01) or STI diagnosis during the previous 12 months (ORa=2.06; 95% CI 1.13 to 3.77). CONCLUSIONS: The incidence of gonorrhoea and syphilis among 15-24-year-olds increased, while HIV infection remained stable but with a high incidence among MSM. Being MSM, having sex with multiple partners and having a diagnosis of an STI in the previous 12 months were factors associated with HIV coinfection.

Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection.

Human immunodeficiency virus (HIV)-1 infection causes severe gut and systemic immune damage, but its effects on the gut microbiome remain unclear. Previous shotgun metagenomic studies in HIV-negative subjects linked low-microbial gene counts (LGC) to gut dysbiosis in diseases featuring intestinal inflammation. Using a similar approach in 156 subjects with different HIV-1 phenotypes, we found a strong, independent, dose-effect association between nadir CD4+ T-cell counts and LGC. As in other diseases involving intestinal inflammation, the gut microbiomes of subjects with LGC were enriched in gram-negative Bacteroides, acetogenic bacteria and Proteobacteria, which are able to metabolize reactive oxygen and nitrogen species; and were depleted in oxygen-sensitive methanogenic archaea and sulfate-reducing bacteria. Interestingly, subjects with LGC also showed increased butyrate levels in direct fecal measurements, consistent with enrichment in Roseburia intestinalis despite reductions in other butyrate producers. The microbiomes of subjects with LGC were also enriched in bacterial virulence factors, as well as in genes associated with beta-lactam, lincosamide, tetracycline, and macrolide resistance. Thus, low nadir CD4+ T-cell counts, rather than HIV-1 serostatus per se, predict the presence of gut dysbiosis in HIV-1 infected subjects. Such dysbiosis does not display obvious HIV-specific features; instead, it shares many similarities with other diseases featuring gut inflammation.

Body image satisfaction and weight concerns among a Mediterranean adult population.

BACKGROUND: People tend to underestimate their current weight and overestimate their height minimizing health risk factors. The aim of this study was to assess body weight satisfaction, acceptance of body image, weight concern and dieting habits among a Mediterranean adult population. METHODS: Cross-sectional survey was carried out (2009-2010) in the Balearic Islands, Spain. A random sample (n = 1081) of young (18-35 y.o.) and middle-aged adults (36-55 y.o.) was interviewed and anthropometrically measured. RESULTS: Women were more dissatisfied being overweight, less dissatisfied being underweight, and more worried about weight gain than men. Middle-aged participants were more dissatisfied with body shape and underestimated body weight than young's. Employed women defined better current weight than unemployed, but unemployed were more worried about body weight gain. Overweight adults were more likely to underestimate their body weight but were also very worried about weight gain and more likely to report current dieting than their leaner counterparts. Active participants self-reported better body weight and were more satisfied with body image than sedentary. CONCLUSIONS: Most of studied population reported body image dissatisfaction, but half of them are not worried about it. Women were more concerned about their body weight status. Practice of physical activity is a positive factor in self-perception. Holistic strategies are needed to avoid promoting unreal bodies, as well as the acceptance of the real body image.

Gut Microbiota Linked to Sexual Preference and HIV Infection.

The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction.

Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers.

OBJECTIVE: Maraviroc (MVC) is a potential candidate for 'on demand' preexposure prophylaxis. In the present study, we evaluated the efficacy of a single oral dose of MVC to prevent ex-vivo HIV-1 infection of rectal tissue in humans. DESIGN AND METHODS: Eight HIV-1-negative healthy volunteers received a single oral dose of MVC (300 or 600 mg), and two additional volunteers received tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 300/200 mg) for 10 days. Rectal biopsies were performed prior to the ex-vivo challenge (day 0), at day 7 (4 h after MVC) or after 10 days with TDF/FTC. Rectal biopsies were infected ex-vivo, and viral inhibition and CCR5 occupancy was analyzed. MVC concentration in plasma and rectal tissue was measured just after biopsy and after viral incubation. RESULTS: Ex-vivo rectal tissue protection with MVC was incomplete in all but two participants, whereas TDF/FTC avoided ex-vivo infection in the two controls. Median dose-normalized concentration of MVC was significantly higher in rectal tissue than in plasma (561.1 and 155.1 ng/ml, respectively). A significant loss of MVC during the virus incubation (about 60%) and a low CCR5 occupancy (approximately 45%) were detected in rectal cells. CONCLUSIONS: An ex-vivo challenge with a single oral dose of MVC does not prevent ex-vivo infection of human rectal mucosa. The lack of prophylactic efficacy observed suggests that 'on demand' MVC preexposure prophylaxis would not prevent rectal HIV-1 transmission.

The prevalence of excessive weight in Balearic Islands' young and middle-aged women and its association with social and socioeconomic factors: a ten-year trend (2000-2010).

BACKGROUND: Knowledge about trends in the socioeconomic patterning of overweight and obesity in women provides insights into the nature of the obesity epidemic. Therefore the aim was to assess a ten-year trend (2000-2010) in the prevalence of excessive weight in Balearic Islands' women and its association with socioeconomic factors. METHOD: Young (18-35 year-old) and middle-aged (36-55 year-old) women were selected from two population-based cross-sectional nutritional surveys carried out in the Balearic Islands, Spain. The participation rate was 80% during 1999-2000 and 92.5% during 2009-2010. Measured weight and height was obtained, and body mass index (kg/m(2)) was classified as follows: overweight (25.0 < 30), obese (≥ 30) and excessive weight (≥ 25). In both surveys, a general questionnaire including questions relating to socioeconomic status factors was used. Logistic regression was used to examine the association of excessive weight with socioeconomic variables and to test the interaction between the survey period and the socioeconomic factors. RESULTS: Overall, while the prevalence of obesity mainly remained stable over the study period, the prevalence of overweight increased from 21.0 to 24.8%. Young women showed an increased prevalence of overweight and excessive weight, from 14.1 to 20.9% and from 20.9 to 28.6%, respectively. Significant differences were not found in middle-aged women. Over the whole period, the incidence of excessive weight was higher among middle-aged and foreign women, but lower in women with a high educational profile and in employment. The prevalence of excessive weight in young women was also around 2.5 times higher in women who were living with at least one child at home. The tendency towards excessive weight in employed women decreased significantly between 2000 and 2010 in the younger age group (OR: 0.42; 95% CI: 0.22-0.82). CONCLUSIONS: No significant increase in the prevalence of overweight/obesity was observed in middle-aged women, with a low level of education being the single socioeconomic variable associated with excessive weight in this target group. Overweight/obesity increased in young women with unemployment being the distinguishing socioeconomic factor associated with this increase.

Ten-Year Trends (2000-2010) of Overweight and Obesity Prevalence among the Young and Middle-Aged Adult Population of the Balearic Islands, a Mediterranean Region.

BACKGROUND AND AIMS: This article aimed at assessing the 10-year trends (2000-2010) in the prevalence of overweight and obesity among the Balearic Islands' adult population. METHODS: Body mass index (BMI, kg/m2) for young (18-35 year-olds) and middle-aged (36-55 year-olds) adults living in the Balearics was calculated. Data represented 1,089 people during 1999-2000 and 1,081 people during 2009-2010. The BMI categories were as follows: normal weight (18.5 < 25), overweight (25.0 < 30) and obese (≥30). RESULTS: Weighted frequency estimates and logistic regression analysis were used to calculate overweight and obesity trends. While the prevalence of overweight and obesity mostly remained stable over the 2000-2010 period, the prevalence of obesity increased from 5.1 to 8.3% in young adults (aged 18-35), a 1.66-fold increase in prevalence (95% CI 1.02-2.70) over the study period. CONCLUSIONS: Total overweight and obesity prevalence remained stable in the Balearic adult population; however, a rising prevalence of obesity has been observed in young adults, which suggests a need to develop and change current strategies in order to reverse the current trends in obesity among this age group.

neo-Clerodane Diterpenoids from Ajuga macrosperma var. breviflora.

Six new naturally occurring ajugarin-like neo-clerodane diterpenoids, ajugaflorins A-F, along with six known compounds [the parent ajugarin I, ajugalides B and C, ajugamarin F4, ajugamacrin E, and ajugatakasin B] were isolated from A. macrosperma var. breviflora. The structures were elucidated by extensive NMR spectroscopic and MS analyses and comparison with data previously reported.

Prevalence and Related Risk Factors of Overweight and Obesity among the Adult Population in the Balearic Islands, a Mediterranean Region.

OBJECTIVE: To assess the prevalence and risk factors of overweight (OW) and obesity (OB) by BMI and abdominal obesity (AO) by waist-to-height ratio, (WHtR) among the Balearic Islands' adult population. METHODS: Cross-sectional nutritional survey carried out in the Balearic Islands (2009-2010). A random sample (n = 1,081) of young (18-35 years) and middle-aged adults (36-55 years) were interviewed and anthropometrically measured. OW (BMI 25.0-29.9 kg/m(2)) and OB (BMI ≥ 30 kg/m(2)) were defined according to WHO criteria. AO was defined as WHtR ≥ 0.5. Socio-economic and lifestyle determinants were considered. RESULTS: The overall prevalence of OW/OB and AO was 29.4% (95% confidence interval (95% CI) 26.9-32.3%), 11.2% (95% CI 9.5-13.2%) and 33.1% (95% CI 30.4-36.0%), respectively. Men showed higher prevalence of OW (35.9%, 95% CI 31.6-40.5%) and AO (37.9%, 95% CI 33.6-42.5%) than women (OW 24.9%, 95% CI 21.7-28.4%; AO 29.7%, 95%CI 26.2-33.4%). Overall prevalence of OB was 11.8% (95% CI 9.1-15.1%) in men and 10.8% (95% CI 8.6-13.5%) in women. Age and no leisure-time physical activity (LTPA) were main risk factors associated with OW/OB and AO. Living with at least one child at home and to be married in men as well as to be unemployed, to be born in South America, and a low level of education in women were associated with AO. CONCLUSIONS: Men showed higher prevalence of OW and AO than women. In both sexes, age is the main risk factor associated with OW/OB and AO; in men also the absence of LTPA plays a significant role.

Neo-Clerodane diterpenoids from Scutellaria altissima.

Nine neo-clerodane diterpenoids, scutaltisins B-G, scupolin I, scutecolumnin C and 11-epi-scutecolumnin C have been isolated from the acetone extract of the aerial parts of Scutellaria altissima. Scutaltisins B-G are new compounds, whereas scupolin I, scutecolumnin C and 11-epi-scutecolumnin C are reported in this species for the first time.

Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected.

The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine-like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders.

Ten-year trends in compliance with the current Spanish nutritional objectives in Balearic Islands adult population (2000-2010).

OBJECTIVE: The Balearic Islands, a well-known Spanish tourist destination for Europeans, is undergoing profound social events, which are reflected in the current food patterns of this population. The aim of this study was to assess 10-year trends (2000-2010) in compliance with the current Spanish nutritional objectives among the adult population of the Balearic Islands. METHODS: Two independent cross-sectional dietary surveys were carried out among the adult population (16-65 y) of the Balearic Islands in 2000 (n = 1200) and 2010 (n = 1350). Dietary habits were assessed by means of two non-consecutive 24-h diet recalls. RESULTS: The proportion of adults complying with the nutritional objectives for consumption of dietary fiber, folate, saturated fatty acids, cholesterol, carbohydrate, and fruit has increased over the 10-y span. In 2009 and 2010, 25% of participants met the nutritional objectives for folate, calcium, monounsaturated fatty acid, cholesterol, and fruit. These results are not affected by age, occupational status, or birthplace. CONCLUSIONS: The percentage of compliers with the Spanish nutritional objectives has increased for 6 to 11 items over the 10-y period. A reduction in saturated fatty acid and cholesterol intake, and an increase in dietary fiber, carbohydrate, fruit, vegetables, folate, and calcium intake should be recommended.

Neo-clerodane diterpenoids from Scutellaria galericulata.

Four neo-clerodane diterpenoids, neoajugapyrin A, scutegalerins A and B and scutecolumnin C have been isolated from the acetone extract of the aerial parts of Scutellaria galericulata. Neoajugapyrin A and scutecolumnin C are reported in this species for the first time, whereas scutegalerins A and B are new compounds. NMR data of neoajugapyrin A ar e discussed i n detail t o support t he proposed revised structure of ajugapyrin A.

A cell-based reporter assay for screening for EcR agonist/antagonist activity of natural ecdysteroids in Lepidoptera (Bm5) and Diptera (S2) cell cultures, followed by modeling of ecdysteroid-EcR interactions and normal mode analysis.

Ecdysteroid signal transduction is a key process in insect development and therefore an important target for insecticide development. We employed an in vitro cell-based reporter bioassay for the screening of potential ecdysone receptor (EcR) agonistic and antagonistic compounds. Natural ecdysteroids were assayed with ecdysteroid-responsive cell line cultures that were transiently transfected with the reporter plasmid ERE-b.act.luc. We used the dipteran Schneider S2 cells of Drosophila melanogaster and the lepidopteran Bm5 cells of Bombyx mori, representing important pest insects in medicine and agriculture. Measurements showed an EcR agonistic activity only for cyasterone both in S2 (EC50=3.3µM) and Bm5 cells (EC50=5.3µM), which was low compared to that of the commercial dibenzoylhydrazine-based insecticide tebufenozide (EC50=0.71µM and 0.00089µM, respectively). Interestingly, a strong antagonistic activity was found for castasterone in S2 cells with an IC50 of 0.039µM; in Bm5 cells this effect only became visible at much higher concentrations (IC50=18µM). To gain more insight in the EcR interaction, three-dimensional modeling of dipteran and lepidopteran EcR-LBD was performed. In conclusion, we showed that the EcR cell-based reporter bioassay tested here is a useful and practical tool for the screening of candidate EcR agonists and antagonists. The docking experiments as well as the normal mode analysis provided evidence that the antagonist activity of castasterone may be through direct binding with the receptor with specific changes in protein flexibility. The search for new ecdysteroid-like compounds may be particularly relevant for dipterans because the activity of dibenzoylhydrazines appears to be correlated with an extension of the EcR-LBD binding pocket that is prominent in lepidopteran receptors but less so in the modeled dipteran structure.